Our continuing efforts to study structure-activity relationships of peptide opioids have resulted in the synthesis of a series of cyclic opioids related to dermorphins and deltorphins. The biological activities of the compounds have been determined and the conformational analyses carried out using 1H-NMR spectroscopy and molecular modelling. The three compounds in the series Tyr-c[D-Orn-Phe-Ala], Tyr-c[D-Lys-Phe-Ala], and Tyr-c[A2bu-Phe-Ala-Leu] are cyclized via a lactam bridge from the side-chain of the residue at the second position with the carboxyl terminus of each compound. The molecules incorporate 12-, 13- and 14-membered rings, respectively. They include a phenylalanine at the third position which is a distinguishing characteristic of dermorphins and deltorphins. The guinea pig ileum and mouse vas deferens assays show that the compounds are highly active at both mu- and delta-opioid receptors. The compounds are all highly effective antinociceptive agents as measured by the intrathecal rat hot plate test. Conformational analyses of the molecules indicate that they can adopt topochemical arrays required for bioactivity at both mu- and delta-receptors which explains their high activity in both guinea pig ileum and mouse vas deferens in vitro assays. The results support our models for mu- and delta-receptor activity for constrained peptide opioids.

The labile disulfide bridge between cysteine residues in naturally occurring peptides can be replaced by lanthionine, as demonstrated by the synthesis of conformation‐ally constrained dipeptide mimetics (see below) based on β,β‐dimethylcyclolanthio‐nines. Their structural features indicate that they represent a novel family of peptidomimetics.

Zur Substitution der labilen Disulfidbrücken zwischen Cysteinresten in natürlichen Peptiden eignet sich Lanthionin (siehe unten), wie die Synthese konformativ rigider Dipeptidmimetica auf der Grundlage von β, β‐Dimethylcyclolanthioninen belegt. Ihre strukturellen Eigenschaften zeigen, daß sie eine neue Familie von Peptidmimetica repräsentieren.

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A model of quantum computation (QC) is compared with a generalized classical computation model, named stochastic ensemble computation (SEnC), in article number https://doi.org/10.1002/qute.201800037 by Jeongho Bang, Jinhyoung Lee, Wonmin Son and co‐workers. SEnC runs in an ensemble consisting of finite copies of single probabilistic entities, and hence is a generalized probabilistic Turing machine. Impossibility of simulating a QC in the SEnC is proved, manifesting “QC is characterized beyond any classical probabilistic computation,” i.e., SEnC ⊆ QC.